It is proposed to apply the synthetic model approach to cytochrome oxidase and oxyhemoglobin in order to gain a molecular level understanding of their fundamental active site chemistry upon interaction with oxygen. The synthetic chemistry involves the preparation of superstructured porphyrins having appended benzimidazole moieties for binding copper in close proximity to heme iron. Picket-fence-type porphyrins with appendages containing H-bonding moieties will quantify the contribution that a distal H-bond can make to the affinity of O2 in oxyhemoglobin models. It is also proposed to grow single crystals of an ordered oxyhemoglobin model so that for the first time, accurate dimensions of the FeO2 moiety can be obtained. Emphasis in all of the studies will be placed on the definitive characterization of analytically pure crystalline materials by X-ray crystallography. Spectroscopist investigations (IR, UV-VIS, EPR, Mossbauer, etc.) and magnetic susceptibility measurements will also be used to characterize materials. The compounds will provide well-defined systems on which to test the validity of recent deductions about the structure of cytochrome oxidase and oxyhemoglobin. The model compounds will be used to gather insight into the mechanisms of hemoprotein interaction with oxygen. A detailed molecular level understanding of hemoproteins must underlie medical approaches to the therapy of their disorders (thalassemias, sickle cell anemia, etc.).